Hearing loss in the aged, presbycusis is the number one communicative disorder of the elderly. Loss of sensory cells (hair cells) in the basal (high pitch) portion of the cochlea (inner early of the peripheral auditory system), and cochlear metabolic problems clearly contribute to presbycusis. Other more recent evidence from our Rochester group reveals that age-related changes in the brain itself (auditory brainstem) are causes of presbycusis. Other more recent evidence from our Rochester group reveals that age-related changes in the brain itself (auditory brainstem) are causes of presbycusis. Other more recent evidence from our Rochester group reveals that age-related changes in the brain itself (auditory brainstem) are causes of presbycusis. These peripheral and central factors result in two main perceptual difficulties: a high-pitch loss in sensitivity and a difficulty of understanding speech in background noise. During the previous funding, significant age-related changes were observed in animals with are-related auditory temporal processing deficits, in the domains of auditory brainstem rewiring and calcium regulatory proteins. In the upcoming grant periods, techniques of molecular neurobiology, immunohistochemistry and biochemistry will be geared towards delineating further the possible neural underpinnings of age-related complex sound processing deficits. Close ties will exist with the Animal Behavior Project (acoustic startle response)-Project 2), the Animal Physiology Project (midbrain evoked potentials and single units-Project 3), and the Animal Core (Wave I & IV ABRs). These neurophysiological and behavioral experiments will evaluate age-related impairments in temporal in temporal processing in young adult CBA mice that may occur due to blocking the GABA circuitry of the inferior colliculus (IC). In Project 4, it is hypothesized based upon our previous findings that activity-dependent changes in calcium-binding proteins will occur as a result of this chemical lesion. In addition, biotinylated-dextran-amine immunohistochemistry will be performed in conjunction with the single-unit neurophysiological mapping experiments of Project 3. Specifically, inputs to the ventrolateral division of the central nucleus of IC will be compared to the age-induced declines in inputs to dorsomedial IC that we have already discovered. The neural bases of age-related deficits in the auditory efferent system will be probed in our mouse animal models using contralateral suppression of otoacoustic emissions. In addition, expression of voltage-gated K channel protein subunits will be examined in young adult, middle age and old CBA and 57 mouse strains to see if they change with age in conjunction with auditory temporal processing declines and knockout mouse functionality. The results of these studies will be utilized to prepare for medical/surgical/technological interventions to increase the quality of life in our elderly population, especially in regard to sensory perception and brain functioning.